Search Results (535)

Background/Objectives: Natural calcium carbonate materials such as Rügen chalk have a long history of use in balneology and rehabilitation, particularly for musculoskeletal disorders, yet their application remains largely confined to traditional, labour-intensive forms such as powders, suspensions, and packs, which limit usability and broader clinical translation. This study aimed to develop an alginate-based solid foam incorporating Rügen chalk and to evaluate how key formulation components influence its structural, mechanical, and thermal properties relevant for therapeutic use. Methods: Alginate–chalk foams were prepared by mechanical mixing of a sodium alginate–Rügen chalk paste with an amino acid-based surfactant, while in situ CO₂ generation from D–glucono–δ–lactone (GDL) induced calcium-mediated alginate gelation and foam stabilization. A central composite design with response surface methodology was used to assess the effects of alginate, chalk, and Perlastan^®–GDL content on foam pH, overrun, firmness, springiness, pore volume, sphericity, pore density, specific internal surface area, and heat-loss time. Foam microstructure was characterized by optical microscopy and microcomputed tomography (µCT), and the thermal conductivity and cooling behaviour of the selected formulation were compared with therapeutic peat. Results: Stable, elastic solid foams with a three-dimensional porous architecture were obtained across the investigated composition range. Foam overrun (30.8–57.1%) was primarily governed by sodium alginate and Rügen chalk concentrations, while firmness (7.4–15.2 N) increased predominantly with alginate content, and springiness remained high (70–78%), indicating good elastic recovery. Response surface modelling and ANOVA confirmed sodium alginate as the dominant factor influencing both mechanical and structural properties, with statistically significant effects on overrun, firmness, springiness, heat loss, porosity, and specific internal surface. µCT analysis revealed that all foam formulations were predominantly composed of fine, closed-cell pores, with over 96% of pores having volumes below 0.5 mm³ and a consistent median pore volume of 0.02 mm³. Structural differences between formulations were governed primarily by pore number and spatial distribution rather than pore size. Strong correlations were identified between µCT-derived parameters, particularly between specific internal surface, porosity, and pore density, confirming that internal architecture is controlled by pore population rather than individual pore dimensions. Thermal analysis demonstrated that the optimized formulation exhibited thermal conductivity comparable to therapeutic peat and maintained clinically relevant temperatures (35–45 °C) for more than one hour. Based on predefined performance criteria (overrun ≥ 50%, firmness ≤ 10 N, heat loss ≥ 120 s), formulation 7 was identified as optimal, combining favourable mechanical properties, structural uniformity and thermal retention. Conclusions: Alginate-based solid foams incorporating Rügen chalk constitute a feasible and tunable platform that combines efficient mineral loading, elastic porosity, and effective heat retention, offering a practical and modern alternative to conventional mineral-based therapeutic applications in balneology and rehabilitation. Full article

Background/Objectives: Motor impairments, including reduced muscular strength and coordination, are commonly reported in children with autism spectrum disorder (ASD) and may negatively affect functional mobility and participation in daily activities. Despite increasing recognition of these challenges, structured resistance training programs for children with ASD remain limited. This study aimed to examine the effects of a 12-week resistance training program on muscular strength and functional performance in children aged 9–11 years with mild ASD. Methods: A selected-group repeated-measures design was employed. Twenty-eight children with specialist-confirmed mild ASD were allocated to an exercise (n = 14) or control group (n = 14) using a strength-matched allocation procedure. The intervention followed established exercise guidelines for youth. Assessments were conducted at baseline, week 6, and week 12 and included handgrip strength, vertical jump height, and 10-m walk time. Non-parametric Friedman tests assessed changes over time, followed by Durbin–Conover post hoc comparisons where appropriate. Effect sizes (r) were calculated. Results: No significant overall time effect was observed for handgrip strength, although a between-group difference favoring the exercise group was observed at week 6. Vertical jump height demonstrated a significant effect over time, with improvements observed in the exercise group from baseline to week 6 and a between-group difference at week 6. Walking time improved significantly across the study period, with improvements observed in both the exercise and control groups. Conclusions: These findings suggest that structured resistance training is a feasible intervention that may support improvements in physical function in children with mild ASD. Resistance training may therefore represent a useful component of exercise programs aimed at improving functional mobility and participation in children with developmental conditions. Full article

Background: This study investigated the relationships among mitochondrial energy metabolism, immune function, and gut microbiota in mice under a fatigued state, providing preliminary evidence for future nutrition-related mechanistic and intervention studies. Methods: Mice were adaptively fed for 4 days and then randomly divided into a normal control group (NC) and a fatigue model group (NM). Immune organ indices, serum IgG levels, thigh muscle ATP content, mitochondrial respiratory chain complex I–IV activities, and gut microbiota composition were assessed using enzyme-linked immunosorbent assay (ELISA), microplate assays, and 16S rRNA gene sequencing. Results: Compared with the NC, the NM showed a significantly reduced spleen index, serum IgG levels, mitochondrial respiratory chain complex I, III, and IV activities, along with reduced ATP content. Regarding gut microbiota, mice in the NM exhibited disordered intestinal villus arrangement, inflammatory cell infiltration in the crypts and muscular layers, and markedly reduced intestinal microbial activity as well as protease and sucrase activities. 16S rRNA sequencing revealed fewer ASVs in the NM, with enrichment of Lactobacillaceae, Limosilactobacillus, and Ligilactobacillus, whereas the NC was characterized by Borkfalkiaceae and Borkfalkia. Linear discriminant analysis effect size (LEfSe) analysis identified Lactobacillaceae, Firmicutes_D, and Lactobacillales as characteristic taxa of the NM. Kyoto Encyclopedia of Genes and Genomes (KEGG) prediction indicated that fatigue-associated microbial functions were mainly related to carbohydrate, amino acid, and lipid metabolism. Correlation and RDA analyses further suggested that alterations in gut microbiota structure were closely associated with mitochondrial energy-related indicators and immune-related parameters. Conclusions: Fatigue was associated with alterations in energy metabolism, immune function, and gut microecology in mice. The “gut microbiota–energy metabolism–immunity” framework may represent a potential association-based framework and provides biological information to support future nutrition-related intervention studies. Full article

Background: Hereditary fibrinogen disorders comprise a rare and heterogeneous group of conditions characterized by highly variable clinical phenotypes, ranging from entirely asymptomatic to severe hemorrhage or paradoxical thrombosis. Within this spectrum, hereditary hypofibrinogenemia (HH) poses a significant obstetrical challenge due to the lack of evidence-based management guidelines during pregnancy. Methods: A scoping review of the literature was conducted to identify reported cases of pregnancies with HH reaching the third trimester. PubMed, Scopus, and Cochrane Library were searched through April 2026 for eligible studies reporting maternal and neonatal outcomes, fibrinogen replacement therapy during pregnancy, and peri- and postpartum management. A complementary LeapSpace search was also performed. Data were extracted using a structured form and owing to the heterogeneity and descriptive nature of the available evidence, results were synthesized narratively. Results: Out of 202 unique records identified, a total of 13 studies, comprising 33 pregnancies, were included. All evidence arose from case reports and small case series, with substantial variability in patient characteristics and clinical management. Successful outcomes are associated with early diagnosis, careful assessment of medical and obstetrical history, and close multidisciplinary surveillance. Maintaining fibrinogen levels above 50–100 mg/dL during pregnancy and ≥150 mg/dL peripartum appeared beneficial. The use of global coagulation assessment tools such as rotational thromboelastometry (ROTEM^®), particularly the FIBTEM^® assay, may support individualized management beyond fibrinogen levels alone; however, up to date it has been incorporated in the management of a single pregnancy. Conclusions: Management of pregnancy in women with HH should be individualized and multidisciplinary, with tailored fibrinogen supplementation strategies to optimize maternal and neonatal outcomes. Small sample sizes and the heterogeneity of the reported results limit the certainty of these findings, requiring further research to establish subtype-specific recommendations and to define additional coagulation parameters that may improve perinatal care. Full article

Nickel ferrite (NiFe₂O₄) is one of the most studied inverse-spinel ferrites because it combines moderate saturation magnetization, comparatively high electrical resistivity, chemical stability, and broad synthesis flexibility. Yet the literature shows that the measured structure and magnetism of NiFe₂O₄ are not intrinsic constants; they evolve strongly with dimensionality, size, thickness, strain state, cation distribution, surface spin disorder, and synthesis pathway. This review develops a unified theoretical and literature-based interpretation of how dimensionality reshapes the structural and magnetic behavior of NiFe₂O₄ across bulk ceramics, nanoparticles, one-dimensional nanostructures, polycrystalline thin films, and ultrathin epitaxial films. The review is anchored in the two uploaded nickel ferrite attachments and expanded using internet-sourced journal literature on spinel inversion, surface effects, mechanochemical synthesis, sputtered and pulsed laser deposited thin films, and epitaxial ultrathin-film anomalies. The central novelty of this article is the formulation of a dimensionality-dependent framework in which the observed magnetic response is governed by a competition among three coupled factors: (i) the cation-distribution function, which controls the A–B superexchange balance and therefore the net ferrimagnetic moment; (ii) the microstructural coherence function, which measures how crystallinity, strain, defects, and anti-phase boundaries preserve or degrade exchange continuity; and (iii) the surface/interface spin-order parameter, which quantifies the loss or reconfiguration of magnetic order at free surfaces and buried interfaces. Within this framework, bulk NiFe₂O₄ behaves as a near-equilibrium inverse spinel with relatively stable magnetization, whereas nanoscale NiFe₂O₄ experiences strong spin canting and finite-size suppression due to the growing fraction of disordered surface spins. Thin films introduce a distinct regime in which strain, texture, anti-phase boundaries, substrate mismatch, and growth kinetics determine both anisotropy and magnetization. In ultrathin epitaxial films, off-equilibrium cation redistribution and interface-controlled electronic reconstruction may even generate magnetization values far above bulk expectations. The review also compares major synthesis routes—solid-state reaction, sol–gel, co-precipitation, hydrothermal growth, reactive milling, combustion, pulsed laser deposition, and radio-frequency sputtering—and explains why each route biases the final dimensionality-dependent properties differently. A set of word-style equations is provided to formalize spinel inversion, finite-size suppression, anisotropy scaling, coercivity trends, and superparamagnetic crossover. Beyond summarizing the field, the review proposes a regime map linking dimensionality to characteristic structural defects and magnetic signatures, and it identifies unresolved questions concerning the true origin of enhanced magnetization in ultrathin NiFe₂O₄, the interplay between anti-phase boundaries and strain, and the distinction between intrinsic inversion changes and extrinsic substrate artifacts. The resulting article offers a submission-ready, originality-focused review that positions dimensionality as the master variable governing structure–magnetism correlations in nickel ferrite. Full article

Background: Insomnia is common among people with mental health conditions and can exacerbate symptoms, impair functioning and negatively impact treatment outcomes. Community mental health services require practical data to quantify the burden of insomnia in routine care and to identify groups at a higher risk of experiencing clinically significant insomnia. Methods: We conducted a retrospective analysis of anonymized routinely collected clinical data from adult psychiatric outpatients attending the Community Mental Health Center in Bra (Department of Mental Health, Asl Cuneo 2, Italy). Consecutive patients were included over a three-month period (1 September to 30 November 2025). Insomnia severity was assessed using the Insomnia Severity Index (ISI). Diagnoses were established by psychiatrists using the Structured Clinical Interview for DSM-5 (SCID-5). Results: The sample included 506 patients (mean age: 45.1 ± 16.7 years; 265 women, 52.4%). The mean ISI total score was 12.18 ± 6.99. Clinically significant insomnia (ISI ≥ 15) was present in 205 out of 506 patients (40.5%), while severe insomnia (ISI ≥ 22) was present in 55 out of 506 patients (10.9%). The ISI score differed across diagnostic groups (ANOVA, F(8, 497) = 2.82, p = 0.0046, η² = 0.043). Post hoc comparisons revealed higher ISI scores in patients with depressive disorders than in those with anxiety disorders (Tukey, p = 0.0056). In a multivariable logistic regression model (outcome: ISI score of at least 15), adjusted for age, sex, education and the complexity of concurrent psychotropic medication (number of medication classes), depressive disorders were associated with clinically significant insomnia (OR: 1.99; 95% CI: 1.07–3.73). Attention deficit hyperactivity disorder (ADHD) also showed higher odds (OR: 3.64; 95% CI: 1.26–10.55). Medication complexity was also associated with an ISI score of at least 15 (OR: 1.43 per additional class; 95% CI: 1.16–1.77). In a sensitivity model additionally adjusting for benzodiazepine prescription (yes/no), benzodiazepine prescription was associated with ISI ≥ 15 (OR 1.82; 95% CI 1.13–2.95), while the estimate for medication complexity was attenuated using this association (OR 1.17; 95% CI 0.90–1.53). The eating disorders group was excluded from multivariable models due to the very small sample size (n = 4). Conclusions: Clinically significant insomnia was prevalent among this sample of psychiatric outpatients, with modest differences in insomnia severity across diagnostic groups. Sensitivity analyses suggested that the signal of medication complexity may be partly accounted for by benzodiazepine prescribing, supporting the cautious interpretation of medication-related correlates in routine cross-sectional data. These findings support routine insomnia screening in psychiatric outpatient care, while prospective studies are needed to clarify directionality and clinical implications. Full article

Video modelling (VM) is widely used as an instructional strategy to support skill acquisition among individuals with autism spectrum disorder (ASD), particularly within visually mediated learning contexts. This systematic review synthesises recent empirical evidence on the effectiveness, limitations, and practical implementation of VM interventions in autism education. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Electronic searches were conducted in Google Scholar and Springer Nature Link, focusing on peer-reviewed empirical studies published between 2020 and 2024. Following screening and eligibility procedures, 20 studies were included in the final synthesis. Most studies employed single-case experimental designs (SCEDs), with fewer using group-based or quasi-experimental approaches. Due to heterogeneity in study designs, participant characteristics, intervention procedures, and outcome measures, findings were synthesised narratively. Across studies, VM interventions were applied across multiple domains, including social communication, academic learning, vocational skills, and daily living routines. The most consistent evidence was observed for structured and procedural skills. However, the evidence base remains limited by methodological variability, small sample sizes, and the predominance of SCEDs, which constrain generalisability. This review provides a domain-based and implementation-informed synthesis of recent VM research, highlighting contextual factors influencing effectiveness. While VM shows promise, conclusions should be interpreted cautiously. Future research with larger samples and more rigorous designs is needed to strengthen the evidence base. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists, originally developed for type 2 diabetes and obesity, have recently attracted interest as potential modulators of addictive behavior. This narrative review summarizes current knowledge on the neurobiological basis, randomized controlled trials, and psychiatric relevance of GLP-1 analogs in substance use disorders. English-language articles available at the time of the search were reviewed between February and April 2026, with emphasis on topics most relevant to psychiatric practice. The literature suggests that GLP-1 signaling influences reward processing, cue reactivity, stress responses, relapse vulnerability, and executive control through actions in the gut–brain axis and mesocorticolimbic circuitry. Early clinical findings are most encouraging in alcohol-related outcomes, including reductions in alcohol cue reactivity, craving, alcohol self-administration, and some measures of heavy drinking, whereas evidence in nicotine dependence is mixed and appears more consistent for limiting post-cessation weight gain than for improving abstinence itself. Evidence for other substance use disorders remains preliminary. Across randomized controlled trials, interpretation is limited by small sample sizes, short follow-up, heterogeneous endpoints, and selective populations. In addition, psychiatric and behavioral safety requires careful attention, particularly regarding rapid weight loss, excessive appetite suppression, restrictive eating, dehydration, and psychological destabilization in vulnerable individuals. At present, GLP-1 receptor agonists should be regarded as promising but unproven adjunctive candidates in addiction psychiatry, warranting further rigorous trials, structured monitoring, and interdisciplinary collaboration. Full article

The efficient adsorption and storage of gases within nanoporous materials are critical for technologies such as adsorbed natural gas systems and energy storage. A paramount goal is to maximize the adsorbent’s gas uptake capacity. However, the fundamental relationship between pore structure and adsorption performance in disordered aerogels remains unclear, hindering rational material design—specifically, where within the complex pore network adsorption predominantly occurs and how the pore size distribution (PSD) should be engineered to enhance capacity. To address this, we conduct molecular dynamics simulations investigating nitrogen adsorption in silica aerogels with tunable PSDs (achieved via tensile deformation) and varied gas–solid interaction strengths (ε). Our results reveal a kinetic-capacity trade-off: microporous-dominated structures saturate rapidly but have limited total uptake, whereas structures with developed mesoporosity (2–10 nm) achieve higher equilibrium capacity via capillary condensation, despite slower kinetics. The interaction strength ε is identified as a key factor governing both capacity and selectivity. Synthesizing these insights, we establish dual design guidelines: to maximize storage capacity, a hierarchical network combining micropores and interconnected mesopores is essential; for optimal reversible performance in cyclic applications like adsorbed natural gas, prioritizing open mesopores with moderately tuned surface chemistry is key. This work clarifies key aspects of the structure–performance relationships and provides evidence-based design guidelines for designing advanced aerogel adsorbents tailored for efficient, low-pressure gas storage. Full article

Background: Alcohol use disorder (AUD) is a major public health concern frequently associated with anxiety and depressive disorders, highlighting the need for innovative and personalised mental health interventions. Virtual reality (VR) has emerged as a digital tool that may support cognitive behavioural therapy (CBT) by enabling immersive and controlled exposure to relevant stimuli. Methods: This scoping review aimed to map how VR is integrated into CBT-oriented interventions for adults with AUD, with a focus on therapeutic mechanisms and their potential relevance for precision digital mental health. The review followed Joanna Briggs Institute methodology and PRISMA-ScR guidelines. Searches were conducted in PubMed, CINAHL, and Psychology and Behavioural Sciences Collection for studies published in the last ten years in English, Portuguese, or Spanish. Two independent reviewers performed screening and data extraction. Results: Eight studies were included, encompassing approaches such as cue exposure, simulation of high-risk environments, and covert sensitisation. The studies explored mechanisms including craving induction and regulation, identification of individual triggers, emotional processing, and enhancement of self-efficacy. The evidence base was characterised by small sample sizes, heterogeneous designs, and limited longitudinal data. Conclusions: This review provides a structured mapping of current applications of VR within CBT frameworks for AUD and highlights key therapeutic mechanisms that may have transdiagnostic relevance. However, the existing evidence remains preliminary, and findings should be interpreted with caution. The results support the exploration of VR within emerging precision digital mental health approaches, while underscoring the need for further rigorous and standardised research. Full article

Essential tremor (ET) is among the most prevalent movement disorders, causing significant impairment in manual dexterity and daily functioning. Although ET affects individuals across the lifespan, exercise intervention research has focused almost exclusively on older adults, leaving young adults, for whom early intervention may prevent long-term neuromuscular deterioration, critically underrepresented. Furthermore, the effects of strength–endurance oriented exercise combined with task-specific motor activities remain insufficiently explored in any ET population. This quasi-experimental pre-test–post-test study investigated the effects of a 6-week progressive strength–endurance and task-specific exercise program on tremor severity, manual dexterity, and upper extremity functional performance in young adult males with ET (n = 18; mean age: 22.6 ± 4.1 years). The 24-session intervention (four sessions/week) combined proximal upper extremity strength–endurance exercises with seven ADL-specific fine motor tasks. Tremor severity was assessed using the Fahn–Tolosa–Marin Tremor Rating Scale (FTMTRS), manual dexterity using the Nine-Hole Peg Test (NHPT), and upper extremity stability using the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST). The Wilcoxon signed-rank test was used for within-group comparisons, with rank biserial correlation (r) and Cohen’s d reported as effect size indices. Significant pre-to-post improvements were observed across nearly all outcome measures, with medium-to-large effect sizes. Spiral drawing performance improved significantly in five of six conditions (r = 0.47–0.62), with the exception of the Spiral left–B task (p = 0.083). Postural tremor, NHPT (both hands), and CKCUEST also showed significant improvements (r = 0.47–0.73). A composite tremor score, integrating all tremor sub-scores, demonstrated a 14.1% overall reduction (p = 0.001, r = 0.83), providing strong evidence of program-wide effectiveness. Session adherence was 95.8%. To our knowledge, this is one of the first studies to show that a structured strength–endurance and task-specific exercise program was associated with reductions in tremor severity and improvements in upper extremity function, specifically in young adults with ET. These findings support the clinical utility of exercise as a non-pharmacological intervention in this underserved population and highlight the importance of early, targeted intervention during young adulthood. Full article

Hair follicle (HF) stem cells are multipotent adult stem cells that play a key role in the hair follicle cycle. However, it remains poorly understood how the outer root sheath (ORS)—specifically, the stem cells in the bulge region of the hair follicle—promotes skin repair. This study aims to investigate the role of bulge stem cells in tissue growth and repair and to determine whether the ORS of transplanted hair follicles can facilitate skin repair. We further seek to elucidate the mechanisms by which bulge stem cells contribute to hair follicle development, regeneration, and skin wound healing. In this study, hair follicle samples were obtained from neonatal mice using microdissection. Hair follicle morphology was assessed by Sirius red staining, H&E staining, and transmission electron microscopy. Immunofluorescence staining was used to detect changes in CD34 and SOX9 protein expression. Additionally, microdissection-based hair follicle transplantation and Western blotting were employed to investigate protein activation and inhibition in the Wnt/β-catenin signaling pathway. The results show that the hair follicle bulge, inner root sheath, and dermal papilla all increase in size as hair follicles grow, with each structure growing relatively rapidly on day 7. Treatment with Teplinovivint effectively inhibits the expression of Wnt/β-catenin signaling pathway-related proteins and hair follicle stem cell markers. Damaged hair follicle tissues cultured in vitro are capable of self-repair. At the transplantation site, the skin gradually closes as the outer root sheath wound heals. In contrast, the central region of the outer root sheath becomes progressively filled with numerous dividing cells and extracellular matrix. The inner portion of the outer root sheath is densely populated with cells, and the markers CD34 and SOX9 are also widely distributed. This indicates that activation of the Wnt/β-catenin signaling pathway enhances the proliferation and differentiation of hair follicle stem cells, thereby promoting hair follicle growth, repair of damaged follicles, and healing of skin wounds. Furthermore, this study demonstrates the feasibility of using transplanted outer root sheath (ORS) to repair skin wounds—specifically, the potential to achieve large-scale hair regeneration from a limited number of hair follicle stem cells—providing a new approach for the clinical treatment of skin injury disorders. Nevertheless, achieving long-term, stable, and scalable clinical translation of ORS stem cells for hair follicle regeneration remains a major challenge. Full article

Feeding and Eating Disorders (FED) require integrated, recovery-oriented care models that extend beyond clinical treatment and incorporate supportive environments capable of enhancing psychosocial well-being. Within this perspective, nature-based and socio-agricultural practices represent promising yet underexplored therapeutic resources, particularly when integrated into spatial planning frameworks. This study develops and tests a Geographic Information Systems (GIS)-based Decision Support System (DSS) that matches the specific therapeutic needs of individuals undergoing treatment for FED with the spatial distribution and characteristics of green and agricultural environments. The research is based on a case study involving the FED care center “Il Pellicano” in Perugia, Italy. Supply-side data were collected from 65 facilities, including 58 social farms, 6 community gardens, and the center’s private garden. Demand-side data were obtained through a questionnaire administered to patients by healthcare professionals, while supply-side attributes were collected through structured interviews with facility managers. The spatial matching process was implemented in a GIS environment using a non-compensatory multi-criteria approach that integrated thematic activities, spatial and/or organizational accessibility, confidentiality, spatial capacity, and environmental settings. The results reveal a substantial mismatch between demand and supply, with the current territorial system satisfying only 37.67% of expressed therapeutic needs. Sensitivity analysis indicates that the main constraints relate to the limited availability of medium-sized, low-attendance, and freely accessible environments. Beyond the local case study, the proposed DSS provides a transferable planning-support tool for designing personalized therapeutic pathways and strengthening the integration between green infrastructure, social farming, and healthcare systems. The study highlights the strategic role of spatial planning in promoting health equity, social inclusion, and community well-being. Full article

Single-domain antibodies (sdAbs) are the smallest antigen-binding antibody (Ab) fragments (12–15 kDa) and have emerged as a versatile therapeutic platform. Their compact size, high solubility, stability, and ability to access cryptic epitopes distinguish them from conventional monoclonal Abs (mAbs) and larger Ab fragments. These properties are particularly attractive in ophthalmology, where molecular size, tissue penetration, and formulation constraints critically influence therapeutic performance. This narrative review summarizes the structural features, engineering strategies, immunogenicity considerations, and production platforms of sdAbs, with a focus on ocular applications. Preclinical studies demonstrate promising efficacy in retinal vascular diseases through targeting of VEGFA, ANG2, TNFα, and complement components, as well as in inflammatory and anterior segment disorders. SdAbs can be formatted as multimeric or Fc-fused constructs to extend intraocular half-life or delivered via gene therapy vectors as a sustained intraocular “biofactory” approach. Notably, recent work demonstrates the feasibility of vector-encoded sdAbs targeting complement C3 in vivo. While challenges remain regarding immunogenicity, pharmacokinetics, and regulatory pathways, the approval of several sdAb-based drugs in other fields underscores their clinical potential. SdAbs represent a promising next-generation modality for ocular therapeutics, enabling innovative strategies beyond conventional antibody formats. Full article

Background/Objectives: Treatment-resistant depression (TRD) remains one of the most urgent unmet needs in psychiatry, while its therapeutic pipeline is evolving rapidly. To characterize current development trajectories, we conducted a registry-anchored mapping of interventional trials in adults with major depressive disorder and treatment resistance (MDD-TRD), with the aim of defining the distribution of intervention types, endpoint choices, and key design features across the active trial landscape. Methods: We systematically searched ClinicalTrials.gov, the EU Clinical Trials Information System, and ISRCTN for interventional MDD-TRD trials registered up to 18 September 2025. After data cleaning and cross-registry deduplication, 237 unique trials were retained. Interventions were categorized through a taxonomy distinguishing device-based neuromodulation, pharmacological strategies, biologic/novel agents, multimodal non-digital combinations, digital–hybrid programs, psychotherapy, and lifestyle interventions, with classification anchored on structured registry intervention tags and whole-word matching across title and intervention text. Primary endpoints were flagged as standard when they explicitly referenced the Montgomery–Åsberg Depression Rating Scale or Hamilton Depression Rating Scale. We also examined developmental phase, sample size, and recurrent methodological features. Results: Device-based neuromodulation accounted for the largest share of the active pipeline (114/237, 48.1%), followed by pharmacological strategies (86/237, 36.3%), biologic/novel agents (16/237, 6.8%), and multimodal non-digital combinations (11/237, 4.6%). Digital–hybrid programs represented a small but distinctive stratum (5/237, 2.1%), with the remaining records comprising lifestyle interventions (3/237, 1.3%) and psychotherapy (2/237, 0.8%). Standard clinician-rated primary endpoints were used in 63.3% of studies. Trial development was concentrated in mid-phase designs, whereas sample sizes were generally modest (median 49; interquartile range, 19–87). Across modalities, increasing attention was directed to durability of response, functioning, and patient-reported outcomes, with adaptive and enrichment-based designs appearing with greater frequency. Conclusions: The contemporary TRD trial ecosystem is structured around two co-active developmental tracks—device-based neuromodulation and pharmacology with novel mechanisms—accompanied by a smaller but measurably expanding biologic/novel stratum and a still-marginal digital–hybrid presence. This registry-based mapping provides a near-real-time overview of the field and may support future harmonization of trial endpoints and design standards. Full article